Premium
Intestinal fungi as regulators of obesity and glucose tolerance
Author(s) -
Al Abdallah Qusai,
Mims Tahliyah,
Watts Sydney,
Pingili Ajeeth,
Bajwa Aman,
Teng Bin,
Makowski Liza,
Han Joan C.,
Pierre Joseph Francis
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09898
Subject(s) - biology , proinflammatory cytokine , cladosporium , microbiome , gut flora , adipose tissue , obesity , microbiology and biotechnology , immunology , aspergillus , endocrinology , inflammation , bioinformatics
Obesity is an emerging health crisis in westernized societies that is associated with numerous comorbidities and chronic diseases. While drivers of obesity are undoubtedly multifactorial, the gut microbiome is a recognized contributor alongside diet, genetics, and environmental factors. In addition to the abundant bacterial populations, other organisms inhabit the gut, such as fungi, but remain underexplored in metabolism research. Our objective was the determine whether intestinal fungi regulate host phenotype in the setting of obesity. We hypothesized that disturbance of intestinal fungal communities negatively shape host metabolic outcomes. We first assessed whether skewing of intestinal fungal populations through low doses of antifungal drugs influenced metabolic phenotype. Antifungals targeting yeasts ‐ including fluconazole (Fluco) and 5‐flurocytosine (5‐FC) ‐ induced body fat increases under high fat diet, while antifungals targeting mold and vehicle controls did not. Metagenomic sequencing confirmed Fluco and 5‐FC elevated molds, including Cladosporium and Aspergillus , while eliminating yeasts, including Candida and Saccharomyces . Further analysis demonstrated Fluco resulted in increased proinflammatory immune markers in peripheral white adipose tissues and reduced glucose tolerance. These effects were not observed in our germ‐free administered Fluco, suggesting intestinal microbes are required for the metabolic alteration. Since molds were elevated by Fluco and 5‐FC treatment, we next colonized germ‐free mice with Cladosporium and observed increased body fat percentage, reduction in glucose tolerance, and increased proinflammatory (M1) macrophage populations in white adipose tissues via flow cytometry, compared with controls. In vitro bone marrow derived macrophages confirmed Cladosporium conidia and mycelia induce M1 macrophage polarization, with mycelia being more immunostimulatory. We conclude that disturbances in gut fungal communities may drive changes in adiposity, glucose tolerance, and immune profiles, with implications for obesity. These findings raise critical questions about the novel, but often overlooked, role of intestinal eukaryotes in obesity and inflammation research and further highlight the need to examine the interkingdom dynamics when studying intestinal microorganisms.